Dr Paul Hiebert P.Hiebert@hull.ac.uk
Lecturer
Activation of Nrf2 in fibroblasts promotes a skin aging phenotype via an Nrf2-miRNA-collagen axis
Hiebert, Paul; Martyts, Anastasiya; Schwestermann, Jonas; Janke, Katharina; Hafner, Jürg; Boukamp, Petra; Mazza, Edoardo; Werner, Sabine
Authors
Anastasiya Martyts
Jonas Schwestermann
Katharina Janke
Jürg Hafner
Petra Boukamp
Edoardo Mazza
Sabine Werner
Abstract
Aging is associated with progressive skin fragility and a tendency to tear, which can lead to severe clinical complications. The transcription factor NRF2 is a key regulator of the cellular antioxidant response, and pharmacological NRF2 activation is a promising strategy for the prevention of age-related diseases. Using a combination of molecular and cellular biology, histology, imaging and biomechanical studies we show, however, that constitutive genetic activation of Nrf2 in fibroblasts of mice suppresses collagen and elastin expression, resulting in reduced skin strength as seen in aged mice. Mechanistically, the “aging matrisome” results in part from direct Nrf2-mediated overexpression of a network of microRNAs that target mRNAs of major skin collagens and other matrix components. Bioinformatics and functional studies revealed high NRF2 activity in aged human fibroblasts in 3D skin equivalents and human skin biopsies, highlighting the translational relevance of the functional mouse data. Together, these results identify activated NRF2 as a promoter of age-related molecular and biomechanical skin features.
Citation
Hiebert, P., Martyts, A., Schwestermann, J., Janke, K., Hafner, J., Boukamp, P., …Werner, S. (2022). Activation of Nrf2 in fibroblasts promotes a skin aging phenotype via an Nrf2-miRNA-collagen axis. Matrix Biology, 113, 39-60. https://doi.org/10.1016/j.matbio.2022.09.002
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 12, 2022 |
Online Publication Date | Sep 20, 2022 |
Publication Date | Nov 1, 2022 |
Deposit Date | Feb 14, 2024 |
Publicly Available Date | Feb 16, 2024 |
Journal | Matrix Biology |
Print ISSN | 0945-053X |
Electronic ISSN | 1569-1802 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 113 |
Pages | 39-60 |
DOI | https://doi.org/10.1016/j.matbio.2022.09.002 |
Keywords | Aging; Skin mechanics; Extracellular matrix; Nrf2; miRNA; Collagen |
Public URL | https://hull-repository.worktribe.com/output/4547460 |
Files
Published article
(6.4 Mb)
PDF
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0
Copyright Statement
©2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
You might also like
A Lysyl Oxidase-Responsive Collagen Peptide Illuminates Collagen Remodeling in Wound Healing
(2024)
Journal Article
Release of miR-29 Target Laminin C2 Improves Skin Repair
(2023)
Journal Article
Targeting NRF2 to promote epithelial repair
(2023)
Journal Article
Downloadable Citations
About Repository@Hull
Administrator e-mail: repository@hull.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search